阿仑膦酸钠和唑来膦酸预防兔激素性股骨头缺血性坏死的作用比较  

Comparison of the preventive effect of alendronate sodium and zoledronic acid on steroid-induced avascular necrosis of the femoral head in rabbits

作　　者：朱和玉[1] 朱兵[1] 孙天胜[1] 常红星[1] 吴军[1] 

机构地区：[1]北京军区总医院骨科,北京100700

出　　处：《中国骨质疏松杂志》2013年第6期591-595,共5页Chinese Journal of Osteoporosis

摘　　要：目的通过建造兔激素性股骨头坏死模型,使用阿仑膦酸钠和唑来膦酸进行干预,观察阿仑膦酸钠和唑来膦酸能否预防兔激素性股骨头缺血性坏死,并比较两种药物的作用强弱。方法健康28周龄新西兰大白兔90只,体重(3.8±0.3)kg,雌雄不限。随机分为阳性对照组(A组)、阿仑膦酸钠组(B组)、唑来膦酸组(C组),每组各30只。各组动物均经耳缘静脉注射10μg/kg大肠杆菌内毒素1次,24 h后于臀肌注射20 mg/kg甲基强的松龙,共3次,每次间隔24 h;B组同时给予阿仑膦酸钠150μg/(kg.d),共45次,颈部皮下注射;C组同时给予唑来膦酸100μg/kg,1次/4 w,共2次,耳缘静脉注射。6 w后取双侧兔股骨头骨组织,沿正中矢状面剖为两半,一半行石蜡包埋、切片,HE染色,计算空骨陷窝率,鉴定股骨头坏死情况。另一半股骨头骨组织再剖为两半,一半提取总RNA,采用实时定量聚合酶链反应(RTQ-PCR)技术检测OPG mRNA和RANKL mRNA的表达水平,并计算OPG/RANKL mRNA比值;一半提取骨蛋白,采用蛋白质免疫印迹法(Western blot)测出OPG和RANKL蛋白表达量,并计算OPG/RANKL比值。结果 A、B、C 3组动物死亡率分别为16.67%(5/30)、13.33%(4/30)、10%(3/30);空骨陷窝率(%)分别为26.33±1.17、20.85±1.47、18.55±2.43;股骨头坏死率分别为76.0%(19/25)、30.77%(8/26)、7.41%(2/27);RTQ-PCR检测股骨头骨组织OPG mRNA分别为0.85±0.086、1.22±0.085、1.62±0.097,RANKL mRNA分别为3.23±0.78、2.84±0.95、1.43±0.93;Western Blot检测股骨头骨组织OPG蛋白表达量分别为0.48±0.09、0.54±0.09、0.74±0.08;RANKL蛋白表达量分别为1.51±0.10、1.23±0.08、0.63±0.08。B、C两组股骨头坏死率低于A组,C组低于B组,差异有统计学意义(P<0.05);B组与C组比较,其OPG mRNA和蛋白表达量较低,RANKL mRNA和蛋白表达量较高,OPG/RANKL比值较低,差异有统计学意义(P<0.05)。结论唑来膦酸和阿仑膦酸钠能够有效预防兔激素性股骨头坏死的发生,其作用与对股�Objective To establish an experimental rabbit model of steroid-induced avascular necrosis of the femoral head, to observe the preventive effect of alendronate sodium and zoledronic acid on steroid-induced avascular necrosis of the femoral head, and to compare the effect of the two drugs. Methods Ninety healthy 28-week adult New Zealand rabbits, with an average weight of 3.8 ± 0. 3 kg, with no restriction of gender, were randomly divided into 3 groups ： positive control group （Group A） , alendronate sodium group （ Group B） , and zoledronic acid group （ Group C）. Each group had 30 rabbits. All the animals were treated with an intravenous injection of 10 p.g/kg lipopolysaccharide for one time. After 24 hours, all the animals were treated with muscle injection of 20 mg/kg methylprednisone for 3 times, with an interval of 24 hours. Rabbits in alendronate sodium group were administered with 150 p.g/kg alendronate sodium via subcutaneous injection per day, lasting for 45 days. Rabbits in zoledronic acid group were treated with 100 p.g/kg zoledronic acid via earintravenous injection for once per 4 weeks, total for 2 times. Six weeks later, the bilateral femoral heads of rabbits were collected and split into halves along the sagittal plane. One half was paraffin embedded, sliced, and stained with HE. Avascular necrosis of the femoral head was evaluated by calculating empty lacuna rate. The other half was cut into two equal parts. Total RNA of the femoral head bone tissue was extracted from one half. OPG and RANKL mRNA expression levels were detected using real-time quantitative polymerase chain reaction （RTQ-PCR）, and the ratio of OPG/RANKL mRNA was calculated. Total protein of the femoral head bone tissue was extracted from the other half, and the expression levels of OPG and RANKL were detected using Western blotting. Then the ratio of OPG/RANKL was calculated. Results The mortality of rabbits in positive control group, alendronate sodium group, and zoledronic acid group was 16. 67% （5/30）, 13.33%

关 键 词：激素 股骨头缺血性坏死 OPG RANKL 

分 类 号：R965[医药卫生—药理学]